eMedicine Specialties > Urology > Stones

Nephrolithiasis: Differential Diagnoses & Workup

Author: J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
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Updated: Sep 28, 2009

Differential Diagnoses

Workup

Laboratory Studies

• Urinalysis
  • Evaluate the urine for evidence of hematuria and infection. Approximately 85% of patients with urinary calculi exhibit gross or microscopic hematuria.
  • An absence of hematuria does not rule out urinary calculi; in fact, approximately 15% of patients with urinary stones do not exhibit hematuria.
• Complete blood cell count
  • In the context of nephrolithiasis, an elevated white blood cell count suggests renal or systemic infection.
  • A depressed red blood cell count suggests a chronic disease state or severe ongoing hematuria.
• Serum electrolytes, creatinine, calcium, uric acid, parathyroid hormone (PTH), and phosphorus studies
  • These are needed to assess a patient's current renal function and to begin the assessment of metabolic risk for future stone formation.
  • A high serum uric acid level may indicate gouty diathesis or hyperuricosuria, while hypercalcemia suggests either renal-leak hypercalciuria (with secondary hyperparathyroidism) or primary hyperparathyroidism.
  • If the serum calcium level is elevated, serum PTH levels should be obtained.
• Twenty-four–hour urine collection for levels of pH, calcium, oxalate, uric acid, sodium, phosphorus, citrate, magnesium, creatinine, and total volume
  • This study is designed to provide more information about the exact nature of the chemical problem that caused the stone. This information is useful not only to allow more specific and effective therapy for stone prevention but also to identify patients with renal calculi who might have other significant health problems. Keep in mind that all of the 24-hour urine chemistry findings may be within the reference range in patients who actively form stones and who are at high risk for stones. In these cases, optimizing the levels is beneficial.
  • The following are objective indications for a metabolic evaluation with a 24-hour urinalysis:
    • Residual calculi after surgical treatment
    • Initial presentation with multiple calculi
    • Initial presentation before age 30 years
    • Renal failure
    • Solitary kidney (including renal transplant)
    • Family history of calculi
    • More than one stone in the past year
    • Bilateral calculi
    • Patient preference: An important consideration in determining whether to perform a 24-hour urine study is the patient's interest. If a patient is strongly motivated to follow a protracted stone-prevention treatment plan (involving diet, supplements, medications, or a combination), obtain the study. If a patient is unlikely or unwilling to follow a long-term treatment plan, a metabolic evaluation is probably unwarranted. Patients have to understand that stone disease is a chronic disease. If they do not commit to helping themselves in behavior modification, dietary changes, or medical compliance, they are prone to more frequent calculi formation.
  • Calcium, oxalate, and uric acid
    • Elevation of the 24-hour excretion rate of any of these 3 components indicates a predisposition to form calculi.
    • Hypercalciuria can be subdivided into absorptive, resorptive, and renal-leak categories based on the results of blood tests and 24-hour urinalysis on both regular and calcium-restricted diets.
      • Depending on the specific subtype, the treatment of absorptive hypercalciuria may include modest dietary calcium restriction, thiazide diuretics, oral calcium binders, or phosphate supplementation.
      • Resorptive hypercalciuria is primary hyperparathyroidism and requires parathyroidectomy, when possible. If parathyroid surgery is not possible, phosphate supplementation is usually recommended.
      • Renal-leak hypercalciuria, which is less common than absorptive hypercalciuria, is usually associated with secondary hyperparathyroidism and is best managed with thiazide diuretics.
    • Another clinical approach to hypercalciuria when hyperparathyroidism has been excluded with appropriate blood tests is avoidance of excessive dietary calcium (usual recommendation, 600-800 mg/d), modest limitation of oxalate intake, and thiazide therapy. If thiazide therapy fails, additional workup (eg, calcium-loading test, more thorough evaluation) may be needed.
    • Indiscriminate dietary calcium restriction is not advantageous and in fact may increase formation of calculi owing to a secondary increase in oxalate absorption. The reduced dietary calcium reduces the oxalate-binding sites in the gastrointestinal tract, increasing the free dietary oxalate and leading to increased oxalate absorption. The final product of this is a net increase in stone production.
    • Hyperoxaluria may be primary (a rare genetic disease), enteric (due to malabsorption and associated with chronic diarrhea or short-bowel syndrome), or idiopathic. Oxalate restriction and vitamin B-6 supplementation are somewhat helpful in patients with idiopathic hyperoxaluria. Enteric hyperoxaluria is the type that is most amenable to treatment; dietary calcium supplementation often produces dramatic results.
    • Calcium citrate is the recommended supplement because citrate tends to further reduce stone formation. Calcium carbonate supplementation is less expensive but does not provide citrate's added benefit. Calcium therapy works as an oxalate binder, reducing oxalate absorption from the intestinal tract. Calcium should be administered with meals, especially those that contain high-oxalate foods. The supplement should not contain added vitamin D because this increases calcium absorption, leaving less calcium in the intestinal tract to bind to oxalate. The optimal 24-hour urine oxalate level is 20 mg/d or less.
    • Hyperuricosuria predisposes to the formation of calcium-containing calculi because sodium urate can produce malabsorption of macromolecular inhibitors or can serve as a nidus for the heterogeneous growth of calcium oxalate crystals. Gouty diathesis, a condition of increased stone production associated with high serum uric acid levels, is also possible. Therapy involves potassium citrate supplementation, allopurinol, or both. In general, patients with pure uric acid stones and hyperuricemia are treated with allopurinol, and those with hyperuricosuric calcium stones are treated with citrate supplementation. The optimal 24-hour urine uric acid level is 600 mg/d or less.
  • Sodium and phosphorus
    • Excess sodium excretion can contribute to hypercalciuria by a phenomenon known as solute drag. Elevated urinary sodium levels are almost always associated with dietary indiscretions. Decreasing the oral sodium intake can decrease calcium excretion, thereby decreasing calcium saturation.
    • An elevated phosphorus level is useful as a marker for a subtype of absorptive hypercalciuria known as renal phosphate leak (absorptive hypercalciuria type III). Renal phosphate leak is identified by high urinary phosphate levels, low serum phosphate levels, high serum 1,25 vitamin D-3 (calcitriol) levels, and hypercalciuria. This type of hypercalciuria is uncommon and does not respond well to standard therapies.
    • The above laboratory tests are confirmatory but are performed only if the index of clinical suspicion is high. Any patient with hypercalciuria who has a low serum phosphorus level and a high-normal or high urinary phosphorus level may have this condition. Repeat laboratories along with a 1,25 vitamin D-3 level are confirmatory. Phosphate supplements are used to correct the low serum phosphate level, which then decreases the inappropriate activation of vitamin D originally caused by the hypophosphatemia. This corrects the hypercalciuria, which is ultimately a vitamin D–dependent function in this condition.
  • Citrate and magnesium
    • Magnesium and, especially, citrate are important chemical inhibitors of stone formation. Hypocitraturia is one of the most common metabolic defects that predispose to stone formation, and some authorities have recommended citrate therapy as primary or adjunctive therapy to almost all patients who have formed recurrent calcium-containing stones. Many laboratories use 24-hour urine citrate levels of 320 mg/d as the normal threshold, but optimal levels are probably closer to the median level (640 mg/d) in healthy individuals. Periodic monitoring of pH with special FDA-approved dipsticks (StoneGard II from www.uridynamics.com) can be very useful to titrate and optimize potassium citrate supplementation. A pH level of 6.5 is usually considered optimal. A pH level over 7.0 should be discouraged, as it prompts calcium phosphate precipitation.
    • Liquid or powder pharmacologic citrate preparations are recommended when absorption is a problem or in cases involving chronic diarrhea. Sustained-release tablets are available and may be more convenient for some patients. Concentrates of lemon juice provide an excellent source of citrate, or, alternatively, large quantities of lemonade can be ingested, which, of course, has the added benefit of providing increased fluid intake.
    • Potassium citrate is the preferred type of pharmacologic citrate supplement, although a potassium/magnesium preparation is under investigation.
    • Magnesium is a more recently recognized inhibitor of stone formation, and the clinical role of magnesium replacement therapy is less well defined than that of citrate.
  • Creatinine
    • Creatinine is the control that allows verification of a true 24-hour sample. Most individuals excrete 1-1.5 g of creatinine daily.
    • Values at either extreme that are not explained by estimates of lean body weight should prompt consideration that the sample is inaccurate.
  • Total volume
    • Patients in whom stones form should strive to achieve a urine output of more than 2 L daily in order to reduce the risk of stone formation.
    • Patients with cystine stones or those with resistant cases may need a daily urinary output of 3 L for adequate prophylaxis.
  • pH: Some stones, such as those composed of uric acid or cystine, are pH-dependent, meaning that they can form only in acidic conditions. Calcium phosphate and struvite only form when the urine pH is alkaline. Although the other parameters in the 24-hour urine usually identify patients at risk of forming these stones, pH studies can be important in monitoring these patients, in optimizing therapy with citrate supplementation, and in identifying occult stone disease in some patients.

Imaging Studies

• Plain abdominal radiography
  • Plain abdominal radiography (also known as a flat plate or kidney, ureter, and bladder [KUB] radiography) is useful for assessing total stone burden, as well as the size, shape, and location of urinary calculi in some patients. It is also helpful in determining the progress of the stone without the need for more expensive tests with greater radiation exposures.
  • Calcium-containing stones (approximately 85% of all upper urinary tract calculi) are radiopaque, but pure uric acid, indinavir-induced, and cystine calculi are relatively radiolucent on plain radiography.
  • When used with other imaging studies, such as a renal ultrasonography or, particularly, CT scanning, the plain film helps provide a better understanding of the size, shape, location, orientation, and composition of urinary stones revealed with these other imaging studies. This may also be helpful in planning surgical therapy and in tracking progress of the stone over time.
• Renal ultrasonography
  • Renal ultrasonography by itself is frequently adequate to determine the presence of a renal stone. The study is mainly used alone in pregnancy or in combination with plain abdominal radiography to determine hydronephrosis or ureteral dilation associated with an abnormal radiographic density believed to be a urinary tract calculus.
  • A stone easily identified with renal ultrasonography but not visible on the plain radiograph may be a uric acid or cystine stone, which is potentially dissolvable with urinary alkalinization therapy.
  • Ureteral calculi, especially in the distal ureter, and stones smaller than 5 mm are not easily observed with ultrasonography.
• Intravenous urography
  • An intravenous urography (IVU) test, also known as an intravenous pyelography (IVP), has been the standard for determining the size and location of urinary calculi up until recently. IVU provides both anatomical and functional information.
  • IVU is very labor intensive and is no longer the standard for the initial evaluation of a patient with a kidney stone. It may fail to reveal alternative pathology if a stone is not discovered, delaying the final diagnosis.
    • Up to 6 hours may be required to complete the study in the presence of severe obstruction.
    • For optimal results, IVU requires a bowel preparation.
    • It involves intravenous injection of potentially allergic and mildly nephrotoxic contrast material.
  • A helical CT scan without contrast material is currently believed to be the best initial radiographic examination for acute renal colic. If positive, KUB radiography is recommended to assist in follow-up and planning.
  • The so-called delayed nephrogram on the IVU is one of the hallmark signs of acute urinary tract obstruction. The relative delay in penetration of intravenous contrast passing through an obstructed kidney elicits this sign. The kidney appears to develop a whitish color, and contrast appearance within the collecting system of the affected renal unit is significantly delayed.
  • IVU is helpful in identifying the specific problematic stone among numerous pelvic calcifications and in establishing that the other kidney is functional. These determinations are particularly helpful if the degree of hydronephrosis is mild and the non-contrast CT scan findings are not definitive. CT scanning with delayed contrast series and thin slices has reduced the need for IVU in the evaluation of problematic ureteral stones.
• Helical CT scanning without contrast material
  • Technological advances in CT scanning allow imaging of the entire abdomen in a single breath hold.
  • When performed with thin slices and without intravenous contrast material, CT scanning is the most sensitive clinical imaging modality for calcifications. Even calculi that are radiolucent on a plain radiograph (except for indinavir-induced stones) are clear and distinct on a CT scan.
  • Contrast is not used in the initial screening study because it makes the entire urinary collecting system appear white on the study, thus masking the stones.
  • CT scanning with contrast, obtained after the noncontrast study, is useful in treatment planning and in distinguishing problematic radio-opacities.
  • At most institutions that offer this examination, CT scanning has replaced IVU for the assessment of urinary tract stone disease, especially for acute renal colic.
  • Adding plain radiography to noncontrast CT scanning increases the value of the study by allowing visualization of the size, shape, and relative position of the stone. The "scout" reconstruction of the CT scan, formatted to look like a plain radiograph, is not nearly as sensitive as a good plain radiograph in detecting calculi; however, if the stone is visible on the "scout" reconstruction, only plain radiography may be needed later to determine if the stone has moved or passed.
  • A lucent stone that is not visible on the KUB radiograph that is clearly visible on the CT scan may indicate a uric acid calculus. This suggests a different diagnosis and therapy (allopurinol and/or urinary alkalinization) than for a calcium stone. For these reasons, many institutions routinely perform KUB radiography whenever renal colic noncontrast CT scanning is performed. The Hounsfield unit density of the calculus on CT scanning can also be useful in predicting whether the stone is composed of uric acid.
  • Advantages of a CT scanning include the following:
    • It can reveal other pathology (eg, abdominal aneurysms, appendicitis, cholecystis).
    • It can be performed quickly.
    • It avoids the use of intravenous contrast materials.
  • Disadvantages of CT scanning include the following:
    • It cannot be used to assess individual renal function.
    • It can fail to reveal some unusual radiolucent stones, such as those caused by indinavir, which are invisible on the CT scan. Because of this possibility, IVUs with contrast should be used for patients taking indinavir.
    • It is relatively expensive.
    • It exposes the patient to a relatively high radiation dose.
    • Precise identification of small distal stones is occasionally difficult.
    • It is not suitable for tracking the progress of the stone over time, supporting the recommendation for KUB radiography along with the CT scan.
• Plain renal tomography
  • Although largely replaced by helical CT scanning without contrast, plain renal tomography is often helpful in finding small stones in the kidneys, especially in patients who are large or obese whose bowel contents complicate observation of any renal calcifications.
  • Tomography does not require extensive preparation and can be performed quickly. In addition, the cost and radiation dosage to the patient are less than with CT scanning.
  • Plain renal tomography is most useful when monitoring a difficult-to-observe stone after therapy or for clarification of stones not clearly detected or identified with other studies.
  • Plain renal tomography is also useful for determining the number of stones present in the kidneys before a stone-prevention program is instituted. This information is used to better differentiate stones formed before therapy began from those formed later.

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